Background: First described in the 1930s by Friedrich Wegener as a rhinogenic granulomatosis, Wegener granulomatosis is a disease of unknown etiology that is characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tract, glomerulonephritis, and a variable degree of small-vessel vasculitis (classic Wegener granulomatosis). A limited form has also been described in which the disease is primarily confined to the lung. In this form, involvement of the kidney, skin, and tracheobronchial tree is distinctly unusual.

Pathophysiology: The etiology of Wegener granulomatosis has not been clearly elicited. Theories have focused on hypersensitivity reactions possibly related to microorganisms; however, to date, a causal relationship has not been established. Regardless, the pathologic demonstration of a necrotizing granulomatous vasculitis without evidence of an infectious etiology is the hallmark of Wegener granulomatosis.

Lung involvement occurs in more than 90% of cases, and examination of biopsy material from the lung generally leads to the diagnosis. Renal involvement occurs in as many as 75% of cases. However, finding evidence of vasculitis in the kidneys is rare, and the histologic diagnosis is usually nonspecific glomerulonephritis. The overall prevalence of tracheal involvement depends on the subset of patients studied and is 15-60%. Isolated laryngotracheal disease is rare. Other common sites of involvement include the paranasal sinuses, skin, and eye, although disease has been documented in virtually all organs and tissues.

Frequency:

• In the US: Wegener granulomatosis occurs with a frequency of approximately 1 case per 30,000 individuals. The diagnosis is presumably becoming more common because of enhanced recognition and testing for the disease (eg, cytoplasmic-antineutrophil cytoplasmic antibody [c-ANCA] testing).

Mortality/Morbidity:

• In the past, Wegener granulomatosis was almost uniformly fatal, with mean survival of 5 months from the time of diagnosis. Currently, treatment with corticosteroids and cyclophosphamide has resulted in a 5-year survival rate approaching 95%.

• The prognosis is poor in untreated individuals.

Race: Wegener granulomatosis is primarily a disease of whites. In a study of 85 patients, Leavitt et al found that 91% of affected individuals were white, whereas only 7% were African American.

Sex: Men are affected more often than women.

Age: The mean patient age at diagnosis is approximately 45 years.

Anatomy: Nodules in Wegener granulomatosis tend to be distributed in an arteriolocentric pattern, but otherwise, the distributions of central and peripheral lesions are equal. The presence of cavitation may be a manifestation of the vasculitis with concomitant infarction and necrosis. Additionally, bronchiectasis, bronchial wall thickening, and interlobular septal thickening and fibrosis have all been described. In children, pulmonary hemorrhage and diffuse airspace abnormalities, rather than pulmonary nodules, are the predominant findings.

Tracheal disease generally occurs in the setting of coexistent nasal or paranasal involvement, and it may be evident only at bronchoscopy. Findings include strictures, the most common manifestation, which usually involves the subglottic trachea, ulcerating tracheobronchitis, and tracheal nodules. Continual bronchial inflammation may lead to a cobblestone pattern.

Clinical Details: The presentation is usually a result of nonspecific signs and symptoms. Systemic complaints such fever, malaise, arthralgias, and weight loss are common. Patients may also complain of upper respiratory symptoms such as persistent sinus pain and/or drainage, mucosal ulcerations, epistaxis, otalgia, and otitis media. Lower respiratory complaints of cough, dyspnea, and hemoptysis may also be present. Hoarseness and stridor are often present when the trachea is involved. Overall, upper or lower respiratory symptoms are present in more than 85% of affected individuals.

Laboratory assessment often reveals an elevation in nonspecific inflammatory markers, with elevations in the erythrocyte sedimentation rate and C-reactive protein level. The c-ANCA result has been shown to be positive in more than 88% of patients with the disease. Renal parameters often show evidence of kidney involvement, while urine analysis frequently shows active sediment. Pathologic confirmation requires the presence of a necrotizing granulomatous vasculitis in the absence of an infectious etiology; samples are best obtained from the lung.

Although the use of the c-ANCA result has largely replaced clinical findings as the means for diagnosing Wegener granulomatosis, clinical criteria were used in the past. The presence of nasal or oral inflammation, abnormal chest radiographic findings, urinary sediment, and suggestive biopsy results are all elements in the clinical diagnosis. The presence of 2 of 4 criteria is 88% sensitive and 92% specific for the diagnosis.

Preferred Examination: Because most patients have respiratory symptoms, chest radiographs are usually obtained first. These may be followed by CT scans of the chest for better delineation of the abnormalities. The nonspecific radiographic findings suggest a differential diagnosis that includes various infections and malignancies. These require further evaluation with biopsy or laboratory evaluation (c-ANCA testing) if the clinical findings are suggestive of Wegener granulomatosis.

Limitations of Techniques: The major limitation of radiographic techniques is the broad differential diagnosis of abnormalities in Wegener granulomatosis. Patients with Wegener granulomatosis may also have normal radiographic findings.

DIFFERENTIALS

Aspergillosis, Thoracic
Aspiration Pneumonia
Blastomycosis, Thoracic
Bronchiolitis Obliterans Organizing Pneumonia
Coccidioidomycosis, Thoracic
Lung Cancer, Non-Small Cell
Lung, Drug-induced Disease
Lung, Metastases
Lung, Trauma
Pneumonia, Atypical Bacterial
Pneumonia, Typical Bacterial
Pneumonia, Viral
Pulmonary Edema, Noncardiogenic
Sarcoidosis, Thoracic
Trachea, Stenosis

Other Problems to be Considered:

Various forms of vasculitis can lead to pulmonary hemorrhage, similar to Wegener granulomatosis.

Pulmonary infarcts, septic pulmonary emboli, metastatic squamous cell carcinoma, fungal infection, and rheumatoid nodules should be considered when the presentation includes multiple solid and cavitary nodules.

The differential diagnosis of tracheal stenosis includes post-intubation stricture or trauma, relapsing polychondritis, sarcoidosis, inflammatory bowel disease, and amyloidosis.

Although the list of differential diagnoses and other problems is exceedingly broad and varied, the differential diagnosis can be usually be limited by evaluating the radiographic findings in the context of the clinical history.

X-RAY

Findings: Pulmonary nodules are the most common chest radiographic manifestation of Wegener granulomatosis and occur in 40-70% of the cases. Nodules may be solitary or multiple and can be cavitated in as many as 50% of patients with nodules. Both thick- and thin-walled cavities may be present. Their size varies, ranging from 1.5-10.0 cm, and the nodules may wax and wane over time.

Airspace opacities are a second manifestation of Wegener granulomatosis. Usually, these findings involve a localized region of consolidation that may occasionally show central necrosis that mimics a lung abscess. Most frequently, this finding is the result of pulmonary hemorrhage, although pulmonary edema secondary to renal involvement may also occur. In one study of children, the airspace pattern was slightly more common. Over time, several of these opacities evolved into thin-walled cavitary lesions.

Other less common pulmonary manifestations include atelectasis and reticular interstitial opacities. Tracheal-bronchial abnormalities are rarely noted on chest radiographs, although tracheal stenosis can occasionally be visualized. Mediastinal adenopathy and pleural abnormalities are uncommon (<10% of cases) and should prompt consideration of other diagnoses.

Degree of Confidence: Because Wegener granulomatosis is a rare disease, its appearance at the top of a differential diagnosis list is unusual. Exceptions involve patients with sinusitis or renal disease and cavitary nodules or those with any of the mentioned radiographic findings and the appropriate clinical and laboratory findings. Most often, radiographs are helpful in confirming the diagnosis and in assessing the extent of pulmonary involvement.

False Positives/Negatives: Chest radiographs may show normal findings in as many as 20% of individuals with Wegener granulomatosis.